ABSTRACT Support is requested for a Keystone Symposia conference entitled Integrated Pathways of Disease in NASH and NAFLD, organized by Drs. Scott L. Friedman, Arun J. Sanyal, Brent A. Tetri, Mary E. Rinella and Christopher R. Shepard. The conference will be held in Santa Fe, New Mexico from January 20-24, 2019. The global prevalence of nonalcoholic fatty liver disease (NAFLD) has risen precipitously over the past two decades in parallel with the worldwide obesity epidemic, however there are no approved therapies. The more advanced form of the disease, non-alcoholic steatohepatitis (NASH) is associated with progressive fibrosis and an increased risk of liver cancer. Despite the growing number of systemic and liver-specific abnormalities identified in patients with NAFLD, a clear hierarchy of the relative importance of specific defects has not emerged. Furthermore, a clear understanding of which individuals are at highest risk for progression to advanced liver disease and cancer remains elusive. Thus, the field lacks an integrated understanding of risk prediction, pathogenesis, and validated biomarkers to predict or track disease progression without reliance on liver biopsies. Therefore, the goals of this meeting are to: 1) Explore genetic and ethnic contributions to NAFLD development; 2) Clarify underlying pathogenic defects in NAFLD and NASH, focusing on the specific contributions of lipotoxicity, the microbiome, innate immune signaling, and drivers of fibrosis; 3) Highlight emerging prognostic and diagnostic biomarkers that are yielding new, more streamlined clinical trial designs that evaluate novel therapies. As a result of this meeting, attendees will gain a more holistic understanding of the unmet needs and new paths to advancing our understanding of NAFLD pathogenesis, diagnosis and therapy. The multidisciplinary nature of the topics and speakers promises to generate novel insights that represent convergent expertise and opinion. In doing so, new paradigms are likely to emerge that greatly inform the expanding number of emerging diagnostic markers and therapeutic agents. The meeting comes at a propitious time at which there is already sufficient basic translational and clinical research to extract important new insights, focus on unmet needs and refine research strategies for the future.